PIK3Cδ expression by fibroblasts promotes triple-negative breast cancer progression

Area of Science:

• Oncology
• Molecular Biology
• Cancer Research

Background:

• The tumor microenvironment significantly influences tumorigenesis.
• Fibroblast-secreted factors play a crucial role in cancer progression.

Purpose of the Study:

• To investigate the role of fibroblast-expressed kinases in triple-negative breast cancer (TNBC).
• To identify potential therapeutic targets for TNBC.

Main Methods:

• High-throughput kinome screening and 3D invasion assays.
• Genetic and pharmacological manipulation of PIK3Cδ.
• Integrated secretomics and transcriptomics analyses.
• In vivo studies using orthotopic and transgenic mouse models.
• Analysis of patient cohorts and TCGA data.

Main Results:

• Fibroblast-expressed PIK3Cδ (f-PIK3Cδ) was identified as a key regulator of TNBC cell invasion.
• f-PIK3Cδ promotes TNBC progression via a paracrine mechanism involving PLGF, BDNF, and NR4A1.
• Inhibition of f-PIK3Cδ reduced tumor growth and metastasis in mouse models.
• f-PIK3Cδ is an independent prognostic factor for overall and disease-free survival in BC patients.

Conclusions:

• Fibroblast-expressed PIK3Cδ is a critical driver of triple-negative breast cancer progression.
• Targeting f-PIK3Cδ represents a promising therapeutic strategy for TNBC.
• f-PIK3Cδ serves as a valuable prognostic biomarker for breast cancer.